PATHOGENESIS OF CALCIUM-CONTAINING GALLSTONES

这项资助的目的是为了定义 含钙的胆结石，以便为他们的 预防和医疗。由于钙盐是一种主要的 所有色素结石的成分，与各种不同的钙沉淀 阴离子(胆红素、碳酸盐、磷酸盐、棕榈酸酯)是一种透明的 胆色素结石形成和生长过程中的必要事件。在……里面 此外，由于所有的胆固醇结石都被发现含有色素 作为第一个主要假说，我们假设，钙 沉淀是胆固醇形成过程中的关键事件 胆结石，因此后者应该被认为是一个由两部分组成的问题：(1) 钙盐沉淀形成团块，以及(2)钙盐沉淀 胆固醇在这个肿块上处于过饱和状态。根据这一点 认为，钙在色素和色素的形成中都起着至关重要的作用 胆固醇结石，延缓或抑制胆固醇结石 用鹅去氧胆酸或熊去氧胆酸溶解。进一步阐明 因此，胆结石的形成需要定义和量化 胆汁中游离钙离子，沉淀的反应物种 “钙敏感”阴离子。第二个主要假设是胆汁酸 阴离子是胆汁中钙离子的主要缓冲剂，游离[Ca++]是 主要由钙与胆盐的络合作用控制。第三大调 假说是，pH在决定哪一种环境中起关键作用 对钙敏感的阴离子会沉淀。第四个假设是 经检测，胆汁钙主要来源于肝脏。 胆小管的分泌物与胆汁酸的分泌物是偶联的。这个 第五，也是最重要的假设是，胆结石有可能 可以通过防止胆汁中的钙沉淀来预防。任何措施 这将减少胆汁中的游离[Ca++]，或者通过减少钙 分泌，或通过增加钙离子络合作用，会减少钙 致石性。拟议的实验将测试这些和其他特定的 假设，并将提供第一个系统的研究：(1)免费 胆汁和胆盐溶液中的[Ca++]：(2)钙离子与胆盐的相互作用； (3)胆汁和胆盐溶液中的二氧化碳体系；(4)钙 碳酸盐和胆红素钙在胆汁中的溶解度。结果是 应该带来新的医疗管理和预防方法 胆石症。

The purpose of this grant is to define the pathogenesis of calcium-containing gallstones in order to develop a rationale for their prevention and medical treatment. Since calcium salts are a major constituent of all pigment stones, precipitation of calcium with various anions (bilirubinate, carbonate, phosphate, 'palmitate') is a clear requisite event in the initiation and growth of pigment gallstones. In addition, since all cholesterol stones have been found to have pigment stone centers, we postulate, as a first major hypothesis, that calcium precipitation is a critical event in the initiation of cholesterol gallstones, so that the latter should be considered a 2-part problem: (1) Precipitation of calcium salts to form a nidus, and (2) precipitation of cholesterol from its supersaturated state on this nidus. According to this view, calcium plays a crucial role in the fomation of both pigment and cholesterol gallstones, and retards or inhibits cholesterol stone dissolution by cheno- or ursodeoxycholic acids. Further elucidation of gallstone formation therefore requires definition and quantification of free Ca++ in bile, the reactive species for precipitation with 'calcium-sensitive' anions. The second major hypothesis is that bile acid anions are the major buffers for Ca++ in bile, and that free [Ca++] is largely governed by calcium complexation with bile salts. The third major hypothesis is that pH plays a key role in determining which of the calcium-sensitive anions will precipitate. The fourth hypothesis to be tested is that the biliary calcium originates primarily at the hepatic canaliculus, and that its secretion is coupled to that of bile acids. The fifth, and most important hypothesis is that gallstones are potentially preventable by prevention of calcium precipitation in bile. Any measure which will reduce free [Ca++] in bile, either by reducing calcium secretion, or by increasing Ca++ complexation, will reduce calcium lithogenicity. The proposed experiments will test these and other specific hypotheses, and will provide the first systematic studies of: (1) Free [Ca++] in bile and bile salt solutions; (2) Ca++-bile salt interactions; (3) The CO2 system in bile and bile salt solutions; and (4) Calcium carbonate and calcium bilirubinate solubilities in bile. The results should lead to new approaches to the medical management and prevention of gallstone disease.